Voltage-gated potassium channels control neuronal excitability and sculpt patterns of neuronal activity. Molecular studies have documented the diversity of subunits and revealed some of the rules governing the association of subunit types. Studies in expression systems have demonstrated the biophysical and pharmacological properties of defined channel types. In contrast, relatively little is known about the composition or functional division of labor of potassium channels in native membranes. We concentrate on the influence of somatic and dendritic Kv channels on computations made by neocortical pyramidal cells to convert synaptic inputs into spike trains. The average rate and timing of action potentials are integral to the functions of neocortical pyramidal cells. In particular, temporal selectivity of pyramidal cells facilitates rhythmic and synchronous activity in cortical circuits, which in turn is important in attentional and perceptual processes in vivo and underlies spread of seizures in epileptic cortex. Most synaptic inputs to pyramidal cells are to dendrites, thus dendritic ion channels are interposed between inputs and the site of spike initiation. Nonlinearities due to activation of a dendritic Ca2+dependent spike initiation zone can lead to intrinsic burst firing in pyramidal cells, which makes synaptic transmission more reliable and facilitates oscillatory behavior. Our previous work indicates that neocortical pyramidal cells express several slowly-inactivating potassium currents. We will concentrate on Kv1 and Kv2 subunits and characterize single channel properties, test functional hypotheses concerning dendritic vs. somatic distribution of channel subunits, and test for a role of Kv2 channels in filtering responses to noisy inputs (to mimic background synaptic inputs). These data are essential for understanding how pyramidal cells process synaptic inputs in health and disease. Abnormalities of Kv1 channels have been implicated in epilepsy and ataxia. Kv2 channels are targets of anesthetic agents, regulators of excitability in many neuronal and nonneuronal cell types, and mediators of apoptosis in cortical neurons. In addition, the distribution and properties of Kv2.1 channels are altered by seizures and ischemia. PUBLIC HEALTH RELEVANCE: These basic studies test how specific potassium channel subunits influence dendritic and somatic computations made by neocortical pyramidal cells to convert inputs into spike trains. These data are essential for understanding how pyramidal cells process synaptic inputs in health and disease. [unreadable] [unreadable]